The effectiveness of percutaneous transluminal coronary angioplasty in the treatment of obstructive arterial disease remains limited by a 25 to 35% incidence of restenosis. The mechanism of restenosis remains unclear, but it is postulated to result from a complex interaction of biological processes including smooth muscle cell migration and proliferation and matrix accumulation. Several mitogens released at the site of arterial injury including platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF) and others may be important modulators of restenosis. Terbinafine (SF 86-327), a squalene epoxidase inhibitor, has been demonstrated to antagonize the in vitro mitogenic response of bovine smooth muscle cells and 3T3 fibroblasts to platelet-derived growth factor and 3T3 fibroblasts to basic fibroblast growth factor. This antagonism was also observed when the incubation media was supplemented with exogenous cholesterol. Furthermore, chronic oral administration of terbinafine was associated with a 40% reduction in neointimal cross sectional area in a single injury rat model of carotid artery balloon catheter injury. The present study evaluated the effect of pretreatment followed by chronic oral terbinafine therapy on restenosis following balloon angioplasty of atherosclerotic femoral arteries in rabbits.